This project includes four major areas of work: development of in vivo tumor models for experimental therapeutic studies; application of these models to evaluation of new natural product anti-tumor drug leads emerging from LDDRD isolation efforts or selective prototype compounds with in vitro selective toxicity; molecular characterization of tumor cell lines used for primary in vitro screening; and, genetic engineering of anti-HIV and anticancer proteins identified in natural product isolation work. The former aspects are closely linked, and project- driven in that the specific cell lines and in vivo models required are defined by individual drug evaluation projects. The molecular characterization work, is more fundamental, and oriented toward developing a base of knowledge that will facilitate understanding and interpretation of in vitro screening data. Since multidrug-resistance may prove limiting to some drug development leads, this complex phenotype has been a particular focus of study. Genetic engineering projects have grown directly out of natural product isolation work and the need to produce proteins of interest for detailed in vivo evaluation studies by either direct administration or gene-therapy approaches.